Quality Management System – Savola Group

Quality Assurance Department –Alexandria Sugar Company (ASC)

Out of specs Procedure

Out of specs Procedure

DOCUMENT NUMBER PR/QD/QC/

ISSUE DATE
ISSUE NUMBER
REVISION NUMBER
NUMBER OF PAGES

Item Prepared by Reviewed by Approved by

Name Mohamed Tawfik Michael Nabil El Hossany Taha

Title QC Supervisor QC Manager Qulaity Sr. Manager
Date
Signatur
e

Pages Revision Status

Page No. Rev. No. Effect. Date

1. Purpose/ Objective:
Investigation of out of specs results of Quality Lab samples
 Quality Management System – Savola Group
Quality Assurance Department –Alexandria Sugar Company (ASC)
Out of specs Procedure

2. Scope:
- This procedure applicable for out of specs results of finished products, Raw material
and process samples.
3. Definitions/Abbreviation:

- OOS: Out Of Specification

4. Responsibility:
- Analyst
- QC Supervisor
- Quality Control manager
5. Procedure:
- lab results are representative to the process cycle of company so it must be
accurate and clear from the mistakes.
- lab staff must be competence to perform this mission well. So, if the lab analyst
obvious that results out of specification limit, abnormal physical characterization,
outlier result immediately inform lab supervisor.
- Lab supervisor begin to investigate the Cause of OOS.
5.1 Lab investigation (phase 1):
- AS OOS arise the first step is initial assessment of lab’s data accuracy and test
instrument malfunction with the same test preparation.
- the responsibility of investigation of OOS is divided between analyst and lab
supervisor.
5.1.1 lab analyst
- Ensure that instrument calibrate and meet performance specification.
- Ensure that system suitability meet its requirement. if not meet it should identify
and collect all data during suspected period and identify the malfunction cause
and correct if possible.
- Check the data for compliance with test specification before spill test
preparations. if results unexpected and no explanation exist, sample preparation
must be retained and inform the supervisor.
- Any errors obvious must be documented as (spilling of sample solution,
incomplete transfer of sample composite, ...)
5.1.2 Lab supervisor
- Data should be assessed promptly to ascertain if the results might be attributed
to laboratory error, or whether the results could indicate problems in the
manufacturing process.
- Immediate Assessment include re-examination of actual solution, glassware and
preparations.
- Assessment steps as the follow:
 Confirm knowledge of analyst for the correct procedure.
 Examine the raw data obtained in analysis with the printout.
 Verify the calculation used to convert raw data into final test results,
appropriate and correct.
 determine if unauthorized or unvalidated changes have been made to
automated calculation methods.
 Confirm the performance of instrument.
 Quality Management System – Savola Group
Quality Assurance Department –Alexandria Sugar Company (ASC)
Out of specs Procedure

 Determine that appropriate reference standards, solvents, reagents, and

other solutions were used and that they met quality control
specifications.
 Evaluate the performance of the test method.
 Fully document and preserve records of this laboratory assessment.
 Ensure that sample retained.
- When evidence of laboratory error remains unclear, a full-scale OOS investigation
should be conducted. And initial laboratory assessment and the following OOS
investigation should be documented fully. (R/QD/QC/)

5.2 Full-Scale OOS (phase 2):

- When the initial assessment does not determine that laboratory error caused the
OOS result and testing results appear to be accurate, a full-scale OOS investigation
using a predefined procedure should be conducted. This investigation may consist
of a production process review and/or additional laboratory work.
- Objective of Full -Scale OOS is to identify OOS Root cause and take appropriate
corrective action and preventive action.
5.2.1 Review of production:
- The investigation should be conducted by all departments that could be
implicated.
- The records and documentation of the manufacturing process should be fully
reviewed to determine the possible cause of the OOS result(s).
- A written record of the review should include the following information.
 A clear statement of the reason for the investigation.
 A summary of the aspects of the manufacturing process that may have
caused the problem.
 The results of a documentation review, with the assignment of actual or
probable cause.
 The results of a review made to determine if the problem has occurred
previously.
 A description of corrective actions taken.
- If this part of the OOS investigation confirms the OOS result and is successful in
identifying its root cause, the OOS investigation may be terminated and the
product rejected which indicate a flaw in product or process design.
5.2.2 Additional Lab testing:
- A number of practices are used during the laboratory phase of an investigation.
These include (1) retesting a portion of the original sample and (2) resampling.

5.2.2.1 Retesting
- This part involves in retesting of a portion of the original sample, sampled from
the same homogeneous material that was originally collected from the lot.
- For a liquid sample, it may be from the original unit liquid product or composite of
the liquid product.
- for a solid sample, it may be an additional weighing from the same sample
composite prepared for the original test.
- The retesting includes investigating test instrument malfunction, possible
handling problem.
- Retesting must perform by another qualified and experience analyst.
 Quality Management System – Savola Group
Quality Assurance Department –Alexandria Sugar Company (ASC)
Out of specs Procedure

- The maximum number of retests to be performed on a sample should be specified

in advance in a written standard operating procedure (SOP). The number may
vary depending upon the variability of the test method employed.
- In case of a clearly identified laboratory error, the retest results would substitute
for the original test result. All original data should be retained, however, and an
explanation recorded. This record should be initialed and dated by the involved
persons and include a discussion of the error and supervisory comments.
5.2.2.2 Resampling
- resampling involves analyzing sample from any additional units collected as part
of the original sample.
- Original sample should be sufficiently large to accommodate additional testing in
the event an OOS result is obtained.
- Resampling should be performed by the same qualified, validated method that
were used for initial sample.
- if the investigation determines that the initial sampling method was inherently
inadequate, a new accurate sampling method must be developed, documented,
and reviewed and approved.
- Full-Scale OOS Should be documented fully. (R/QD/QC/)
5.2.3 Reporting test results:
- Practices used in reporting and interpretation of test results include (1) averaging
and (2) outlier tests.
5.2.3.1 Averaging
- Involve to take average of replication of samples results. may be appropriate or
inappropriate
5.2.3.1.1 Appropriate use
- Averaging data can be a valid approach, but its use depends upon the sample and
its purpose. For example, in an optical rotation test, several discrete
measurements are averaged to determine the optical rotation for a sample, and
this average is reported as the test result.
- If the sample can be assumed to be homogeneous, using averages can provide a
more accurate result.
- If replication technique used to report the average of this replicates it should be
determine specific number of replicates and acceptance limit of variability are
written in approved test method.
5.2.3.1.2 Inappropriate use
- Averaging has the disadvantage of hiding variability among individual test results.
For this reason, all individual test results should normally be reported as separate
values.
- Averaging can also conceal variations in different portions of a batch, or within a
sample.
- Relying on averages of such data can be particularly misleading when some of
the results are OOS and others are within specifications. So It is critical that the
laboratory provide all individual results for evaluation and consideration.

5.2.3.2 Outlier test

- Outlier value: a value may be obtained that is markedly different from the others
in a series obtained using a validated method.
 Quality Management System – Savola Group
Quality Assurance Department –Alexandria Sugar Company (ASC)
Out of specs Procedure

- The CGMP regulations require that statistically valid quality control criteria include
appropriate acceptance and/or rejection levels.
- An outlier may result from a deviation from prescribed test methods, or it may be
the result of variability in the sample
- Outlier test is only a statistical analysis of the data obtained from testing and
retesting. It will not identify the cause of an extreme observation and, therefore,
should not be used to invalidate the suspect result.
- Outlier test should be written into SOPs for data interpretation and be well
documented. The SOPs should include the specific outlier test to be applied with
relevant parameters specified in advance.
5.2.4 CONCLUDING THE INVESTIGATION
- To conclude the investigation, the results should be evaluated, the batch
quality should be determined.
5.2.4.1 Interpretation of Investigation Results.
- Initial OOS Results doesn’t mean the batch fail and must be rejected, but
OOS results, finding and retest results should be investigated and interpreted
to decide if batch release or reject.
- In case the investigation reveals a cause and the OOS Result invalidate, this
result shouldn’t used to evaluate the batch/lot quality.
- In case the OOS results caused by factor affecting the batch quality, the
results should be used in evaluating the batch/lot.
- In the case of OOS confirmed the investigation changes from an OOS
investigation into a batch failure investigation, which must be extended to
other batches or products that may have been associated with the specific
failure.
- In the case of inconclusive investigation lab might still ultimately decide to
release the batch.
5.2.4.2 Cautions
- In case of individual results (to produce a single reportable result), some of
the individual results are OOS , some are within specification, and all are
within the known variability of the method, the passing results are not
represent the true value for the sample, so firm should be take the side of
caution and treat the reportable average of these values as an OOS result
- In case of result is low, but within specifications, should also raise a concern.
One cause of the result could be that the batch/lot hasn’t homogenous well.
- all records pertaining to the OOS test result should be retained. Records must
be kept of complete data derived from all tests performed to ensure
compliance with established specifications and standards.
- After investigation of root cause of OOS, OOS register in OOS tracker
6. FORMS:
6.1 OOS Investigation Protocol
R/QD/QC/
6.2 OOS Tracker R/QD/QC/
7. REFERENCES:
 Quality Management System – Savola Group
Quality Assurance Department –Alexandria Sugar Company (ASC)
Out of specs Procedure

7.1 Guidance for Industry Investigating Out-of-Specification (OOS) Test Results for
Pharmaceutical Production (October 2006)